Hexadecyl 2-ethylhexanoate

Endpoint summary

Description of key information

Skin irritation: not irritating
Eye irritation: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Oct 1991 - 29 Oct 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrussen, Chbb: HM

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany.
- Age at study initiation: approx. 9 months
- Weight at study initiation: approx. 2540 g
- Housing: individual
- Diet: Ssniff rabbit diet K4, Ssniff GmbH, Soest, Germany; ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 75
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

14 days
Reading time points: 1, 24, 48, 72 h and 7 and 14 days after exposure

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on the left or right flank
- Type of wrap if used: gauze patch covered with an adhesive air- and vapor-permeable patch and fixed by using a hypoallergenic adhesive gauze-bandage.

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Table 1: Evaluation of the dermal reaction

Skin effect	Erythema					Edema
	1h	24h	48h	72h	Mean^a	1h	24h	48h	72h	Mean^a
Animal No. #1	1	1	1	2	1.3	1	1	1	2	1.3
#2	1	1	2	2	1.7	1	1	1	2	1.3
#3	1	1	2	3	2.0	1	1	1	2	1.3

^amean of readings at 24, 48 and 72 hours

 

Skin effect	days after exposure
	7	14
Animal No. #1	i b S	+
#2	i b S	+
#3	i b S	+

i = irreversible

b = brownish

S = eschar

+ = reversible

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Oct 1991 - 31 Oct 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrussen, Chbb: HM

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany.
- Age at study initiation: approx. 9 months
- Weight at study initiation: approx. 2510 g
- Housing: individual
- Diet: Ssniff rabbit diet K4, Ssniff GmbH, Soest, Germany; ad libitum
- Water: tap water; ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated left eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, the eyes were thoroughly rinsed with tap water.
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Table 1: Evaluation of the eye reaction

Rabbit No.	Scoring [h]	Cornea	Iris	Conjunctiva
				Redness	Chemosis
1	1	0	0	1	0
	24	0	0	1	0
	48	0	0	1	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0.0	0.0	0.7	0.0
2	1	0	0	1	1
	24	0	0	1	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0.0	0.0	0.3	0.0
3	1	0	0	1	1
	24	0	0	1	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0.0	0.0	0.3	0.0

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

Irritation to skin by hexadecyl 2-ethylhexanoate was evaluated in a GLP study performed in accordance with OECD guideline 404 (Steiling, 1991). The flank skin of three Kleinrussen rabbits were treated with 0.5 mL of the test substance under semiocclusive conditions for 4 h. The readings 24, 48 and 72 hours later revealed mean erythema scores from 1.3 to 2 in the three animals and a mean edema score of 1.3 in all animals, respectively. All skin effects were fully reversible within the 14 days observation period. Based on these results, no skin irritation by hexadecyl 2-ethylhexanoate was found.

Similar results were found in another study performed according to OECD guideline 404, where only limited data were available (Bouffechoux, 1996). Three New-Zealand breed rabbits were treated with hexadecyl 2-ethylhexanoate on shaved and abraded skin sites. Readings were performed 1, 24, 48 and 72 hours and 7 days after application. The mean scores over 24, 48 and 72 hours were 1.0, 1.7, and 1.7 for erythema and 0.0, 0.7, and 0.7 for edema. Erythema and edema scores were fully reversible within 72 h. The results were only given as the sum of scoring values from intact and scarificed skin sites. 

Eye irritation

Eye irritation was evaluated in a GLP study performed according to OECD guideline 405 (Steiling, 1991). 0.1 mL of hexadecyl 2-ethylhexanoate was instilled into the eyes of three Kleinrussen rabbits and was removed by washing with water after 24 h of treatment. While the mean scores after 24, 48 and 72 h for conjunctivae were between 0.3 and 0.7 in the three animals, the mean scores for cornea, iris and chemosis were 0, respectively. Thus, hexadecyl 2-ethylhexanoate was found to be not irritating to eyes.

Another study was also conducted according to OECD guideline 405, but only limited data are available (Bouffechoux, 1996). The eyes of three New-Zealand breed rabbits were single treated with hexadecyl 2-ethylhexanoate and were scored 1, 24, 48 and 72 h and 7 days after treatment. The results were mean conjunctivae scores of 0.3 in all animals while the effects were fully reversible within 48 h. The mean scores for cornea and iris were 0 in all animals, respectively. Thus, this study found hexadecyl 2-ethylhexanoate to be not irritating to eyes.

 

Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data to assess skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.